AIM: To study in vitro release and in vivo effect of four different types o
f sustained-release naltrexone microspheres on, morphine analgesia. METHODS
: Release of naltrexone from four types of biodegradable micro-spheres was
investigated by HPLC. Their antagonist effects on morphine analgesia were o
bserved using mouse hot-plate procedure. RESULTS: Poly latide-co-glycolide
(PLGA) composition had a remarkable effect on naltrexone release from micro
spheres and its antagonism towards morphine analgesia. Two formulations of
PLGA 50:50 formulation released more than 80 % of total naltrexone and lost
their antagonism by 8 d. The PLGA 75:25 formulation with 20 % and 30 % dru
g loadings did not release 95 % of total drug and lose antagonism until 40
d and 30 d, respectively. Increasing the drug loading enhanced naltrexone r
elease from microspheres and seemed to shorten the analgesic antagonistic e
ffect of naltrexone. CONCLUSION: Antagonism by naltrexone microspheres towa
rds morphine analgesia correlates well with the drug release in vitro.